Amblyopia In Adults Research Articles

Treating Amblyopia in Adults With Interactive Video Games

Treating Amblyopia in Adults With Interactive Video Games

Posterior chamber phakic intraocular lens for the correction of high myopic anisometropic amblyopia in adults.

This study aims to evaluate the clinical results of posterior chamber implantable collamer lens (ICL) implantation in adults with high myopic anisometropic amblyopia. Thirteen patients aged 27.04±7.24y (range 19.2 to 42.5) were studied. ICL implantation was performed in 13 amblyopic eyes. The mean myopic anisometropia was significantly dropped from -10.70±3.02 D preoperatively to +0.09±1.67 D at 1mo postoperatively. The logMAR CDVA at 3d, 1, 3 and mean 9mo postoperatively improved by a mean of 1.69, 2.50, 3.01 and 3.00 lines and gained more than 2 lines accounted for 23.08% (3 eyes), 41.67% (5 eyes), 63.63% (7 eyes) and 55.56% (5 eyes), respectively. The contrast sensitivity of amblyopic eyes was significantly increased after surgery. Four patients partially recovered near stereopsis (400″ to 100″). There was no severe complications were observed. ICL implantation alone can improve vision, contrast sensitivity, and partial restoration of binocular vision in adult patients with high myopic anisometropia.

Unilateral Application of Cathodal tDCS Reduces Transcallosal Inhibition and Improves Visual Acuity in Amblyopic Patients.

Objective: Amblyopia is a neurodevelopmental disorder characterized by visual acuity and contrast sensitivity loss, refractory to pharmacological and optical treatments in adulthood. In animals, the corpus callosum (CC) contributes to suppression of visual responses of the amblyopic eye. To investigate the role of interhemispheric pathways in amblyopic patients, we studied the response of the visual cortex to transcranial Direct Current Stimulation (tDCS) applied over the primary visual area (V1) contralateral to the “lazy eye.”Methods: Visual acuity (logMAR) was assessed before (T0), immediately after (T1) and 60’ following the application of cathodal tDCS (2.0 mA, 20’) in 12 amblyopic patients. At each time point, Visual Evoked Potentials (VEPs) triggered by grating stimuli of different contrasts (K90%, K20%) were recorded in both hemispheres and compared to those obtained in healthy volunteers.Results: Cathodal tDCS improved visual acuity respect to baseline (p < 0.0001), whereas sham polarization had no significant effect. At T1, tDCS induced an inhibitory effect on VEPs amplitudes at all contrasts in the targeted side and a facilitation of responses in the hemisphere ipsilateral to the amblyopic eye; compared with controls, the facilitation persisted at T2 for high contrasts (K90%; Holm–Sidak post hoc method, p < 0.001), while the stimulated hemisphere recovered more quickly from inhibition (Holm–Sidak post hoc method, p < 0.001).Conclusions: tDCS is a promising treatment for amblyopia in adults. The rapid recovery of excitability and the concurrent transcallosal disinhibition following perturbation of cortical activity may support a critical role of interhemispheric balance in the pathophysiology of amblyopia.

F142. Corpus callosum and amblyopia: New evidence for an old debate

Introduction Amblyopia is a neurodevelopmental disorder characterized by visual acuity and contrast sensitivity loss, refractory to pharmacological and mechanical treatments in adulthood. In animal models, the corpus callosum (CC) plays a critical role in the development of the ocular dominance, thus strengthening the hypothesis of an involvement of both striate and extrastriate areas in the pathogenesis of amblyopia. To investigate the role of interhemispheric pathways in amblyopia, we studied the response of the visual cortex to transcranial Direct Current Stimulation (tDCS) applied over the primary visual area (V1) contralateral to the amblyopic eye. Methods Visual evoked potentials (VEPs) triggered by grating stimuli of different contrasts (K90%, K50%, K20%) were recorded in both hemispheres before and after inactivation of the occipital cortex of one side via cathodal tDCS (2.0 mA, 20′). VEPs were recorded before (T0), immediately after (T1) and 60′ following tDCS (T2). The display was either centered on the vertical meridian (central stimulation) or positioned in the right hemifield (with its inner edge at a distance of 1 degree from the fixation point). Visual acuity was tested at each time interval, to assess behavioral changes between active and sham stimulation. Results Cathodal tDCS improved visual acuity respect to baseline (recovery of 8.4 ± 3.3 letters, Holm-Sidak post hoc method p Conclusion tDCS is a promising treatment for amblyopia in adults. The rapid recovery of excitability and the persistent transcallosal disinhibition following perturbation of cortical activity strongly supports a critical role of interhemispheric balance in the pathophysiology of amblyopia.

Optical treatment of amblyopia in older children and adults is essential prior to enrolment in a clinical trial.

Optical treatment alone can improve visual acuity (VA) in children with amblyopia, thus clinical trials investigating additional amblyopia therapies (such as patching or videogames) for children require a preceding optical treatment phase. Emerging therapies for adult patients are entering clinical trials. It is unknown whether optical treatment is effective for adults with amblyopia and whether an optical correction phase is required for trials involving adults. We examined participants who underwent optical treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO) clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in three age groups (7 to 12, 13 to 17, or ≥18 years), and had unilateral amblyopia due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30-1.00 logMAR (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on cycloplegic refraction to fully correct any anisometropia. VA was assessed using the electronic visual acuity testing algorithm (e-ETDRS) test and near stereoacuity was assessed using the Randot Preschool Test. Participants were assessed every four weeks up to 16 weeks, until either VA was stable or until amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant ineligible for the trial. Eighty participants (mean age 24.6 years, range 7.6-55.5 years) completed four to 16 weeks of optical treatment. A small but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR was observed (S.D. 0.08 logMAR; paired t-test p < 0.0001). Twenty-five participants (31%) improved by ≥1 logMAR line and of these, seven (9%) improved by ≥2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual improvements were not associated with age, presence of strabismus, or prior occlusion treatment. Two adult participants withdrew due to intolerance to anisometropic correction. Sixteen out of 80 participants (20%) achieved better than 0.30 logMAR VA in the amblyopic eye after optical treatment. Nine of these participants attended additional follow-up and four (44%) showed further VA improvements. Improvements from optical treatment resulted in one-fifth of participants becoming ineligible for the main clinical trial. Studies investigating additional amblyopia therapies must include an appropriate optical treatment only phase and/or parallel treatment group regardless of patient age. Optical treatment of amblyopia in adult patients warrants further investigation.

Treating amblyopia in adults with prosthetic occluding contact lenses.

To investigate the feasibility, effectiveness and acceptability of using prosthetic occluding contact lenses (OCLs) to treat moderate amblyopia in adults and of the role of the multifocal visual evoked potential (mfVEP) as a predictor of postamblyopic therapy. A comparative, prospective, interventional, case series pilot study with amblyopic adults (mean age: 40years, range 20-50years) allocated into two intervention groups: eye patching and OCL. The primary outcome variable was logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and secondary outcomes were mfVEP amplitude and latency and patients' health-related quality of life National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Significant improvements in pre- to postamblyopic therapy BCVA were seen at 1.5months in the OCL group [0.29 logMAR, 95% confidence interval (CI): 0.10-0.47 versus 0.11 logMAR, 95% CI: 0.02-0.19; p<0.001] and eye patching group (0.29 logMAR, 95% CI: 0.17-0.40 versus 0.18 logMAR, 95% CI: 0.12-0.23; p<0.01). Post-treatment BCVA was inversely related to age (R: 0.009, 95% CI: -0.02 to -0.001; p=0.04) and the presence of strabismus (R: -0.3, 95% CI: -0.434 to -0.17; p=0.001). No significant changes in the number and size of the abnormal mfVEP amplitude and latency defects were observed after occlusion. The NEI VFQ-25 composite score showed significant improvement in the OCL users at 12months compared to eye patching. Significant vision improvement can be achieved, making occlusion with OCLs an effective and more acceptable therapy for adults with amblyopia.

Binocular treatment of amblyopia using videogames (BRAVO): study protocol for a randomised controlled trial.

BackgroundAmblyopia is a common neurodevelopmental disorder of vision that is characterised by visual impairment in one eye and compromised binocular visual function. Existing evidence-based treatments for children include patching the nonamblyopic eye to encourage use of the amblyopic eye. Currently there are no widely accepted treatments available for adults with amblyopia. The aim of this trial is to assess the efficacy of a new binocular, videogame-based treatment for amblyopia in older children and adults. We hypothesise that binocular treatment will significantly improve amblyopic eye visual acuity relative to placebo treatment.Methods/designThe BRAVO study is a double-blind, randomised, placebo-controlled multicentre trial to assess the effectiveness of a novel videogame-based binocular treatment for amblyopia. One hundred and eight participants aged 7 years or older with anisometropic and/or strabismic amblyopia (defined as ≥0.2 LogMAR interocular visual acuity difference, ≥0.3 LogMAR amblyopic eye visual acuity and no ocular disease) will be recruited via ophthalmologists, optometrists, clinical record searches and public advertisements at five sites in New Zealand, Canada, Hong Kong and Australia. Eligible participants will be randomised by computer in a 1:1 ratio, with stratification by age group: 7–12, 13–17 and 18 years and older. Participants will be randomised to receive 6 weeks of active or placebo home-based binocular treatment. Treatment will be in the form of a modified interactive falling-blocks game, implemented on a 5th generation iPod touch device viewed through red/green anaglyphic glasses. Participants and those assessing outcomes will be blinded to group assignment. The primary outcome is the change in best-corrected distance visual acuity in the amblyopic eye from baseline to 6 weeks post randomisation. Secondary outcomes include distance and near visual acuity, stereopsis, interocular suppression, angle of strabismus (where applicable) measured at baseline, 3, 6, 12 and 24 weeks post randomisation. Treatment compliance and acceptability will also be assessed along with quality of life for adult participants.DiscussionThe BRAVO study is the first randomised controlled trial of a home-based videogame treatment for older children and adults with amblyopia. The results will indicate whether a binocular approach to amblyopia treatment conducted at home is effective for patients aged 7 years or older.Trial registrationThis trial was registered in Australia and New Zealand Clinical Trials Registry (ACTRN12613001004752) on 10 September 2013.

Amblyopia update: new treatments.

This review article is an update on the current treatments for amblyopia. In particular, the authors focus on the concepts of brain plasticity and their implications for novel treatment strategies for both children and adults affected by amblyopia. A variety of strategies has been developed to treat amblyopia in children and adults. New evidence on the pathogenesis of amblyopia has been obtained both in animal models and in clinical trials. Mainly, these studies have challenged the classical concept that amblyopia becomes untreatable after the 'end' of the sensitive or critical period of visual development, because of a lack of sufficient plasticity in the adult brain. New treatments for amblyopia in children and adults are desirable and should be encouraged. However, further studies should be completed before such therapies are widely accepted into clinical practice.

Perceptual learning treatment of amblyopia in adults

Perceptual learning treatment of amblyopia in adults

Assessment of the Density of Suppression to Identify Risk of Intractable Diplopia in the United Kingdom

ABSTRACTBackground/Aims: Occlusion used to treat amblyopia towards the end of the developmental component of the critical period gives a risk of inducing intractable diplopia. In the United Kingdom, the density of suppression is assessed via the Sbisa/Bagolini filter bar, but there is very little research evidence to guide clinical practice or interpretation of the tests used. The aims of this study were to determine current practice and estimate the incidence of intractable diplopia following amblyopia treatment.Methods: Current practice and incidence of intractable diplopia following amblyopia were determined via a questionnaire distributed to head orthoptists in every eye department in the United Kingdom. The questionnaire explored testing and test conditions, interpretation of the test results, and cases of intractable diplopia over the last 5 years.Results: There was considerable variation in clinical practice of the measurement of the density of suppression and interpretation of the results to guide the treatment of amblyopia. The minimum age of patients taking the test ranged from 2 to 8 years and the minimum filter considered still safe to continue treatment ranged from 4 to 17. It is estimated there were 24 cases of intractable diplopia over the last 5 years.Conclusion: The issue of intractable diplopia and amblyopia treatment is likely to become increasingly important as there appears to be greater plasticity and scope to treat amblyopia in teenagers and adults than was previously thought. Lack of knowledge of how to evaluate the risk may lead to more cases of intractable diplopia or alternatively treatment being withheld unnecessarily.

Optimization of visual training for full recovery from severe amblyopia in adults.

The severe amblyopia induced by chronic monocular deprivation is highly resistant to reversal in adulthood. Here we use a rodent model to show that recovery from deprivation amblyopia can be achieved in adults by a two-step sequence, involving enhancement of synaptic plasticity in the visual cortex by dark exposure followed immediately by visual training. The perceptual learning induced by visual training contributes to the recovery of vision and can be optimized to drive full recovery of visual acuity in severely amblyopic adults.

"Global" visual training and extent of transfer in amblyopic macaque monkeys.

Perceptual learning is gaining acceptance as a potential treatment for amblyopia in adults and children beyond the critical period. Many perceptual learning paradigms result in very specific improvement that does not generalize beyond the training stimulus, closely related stimuli, or visual field location. To be of use in amblyopia, a less specific effect is needed. To address this problem, we designed a more general training paradigm intended to effect improvement in visual sensitivity across tasks and domains. We used a "global" visual stimulus, random dot motion direction discrimination with 6 training conditions, and tested for posttraining improvement on a motion detection task and 3 spatial domain tasks (contrast sensitivity, Vernier acuity, Glass pattern detection). Four amblyopic macaques practiced the motion discrimination with their amblyopic eye for at least 20,000 trials. All showed improvement, defined as a change of at least a factor of 2, on the trained task. In addition, all animals showed improvements in sensitivity on at least some of the transfer test conditions, mainly the motion detection task; transfer to the spatial domain was inconsistent but best at fine spatial scales. However, the improvement on the transfer tasks was largely not retained at long-term follow-up. Our generalized training approach is promising for amblyopia treatment, but sustaining improved performance may require additional intervention.

Mechanisms of recovery of visual function in adult amblyopia through a tailored action video game.

Amblyopia is a deficit in vision that arises from abnormal visual experience early in life. It was long thought to develop into a permanent deficit, unless properly treated before the end of the sensitive period for visual recovery. However, a number of studies now suggest that adults with long-standing amblyopia may at least partially recover visual acuity and stereopsis following perceptual training. Eliminating or reducing interocular suppression has been hypothesized to be at the root of these changes. Here we show that playing a novel dichoptic video game indeed results in reduced suppression, improved visual acuity and, in some cases, improved stereopsis. Our relatively large cohort of adults with amblyopia, allowed us, for the first time, to assess the link between visual function recovery and reduction in suppression. Surprisingly, no significant correlation was found between decreased suppression and improved visual function. This finding challenges the prevailing view and suggests that while dichoptic training improves visual acuity and stereopsis in adult amblyopia, reduced suppression is unlikely to be at the root of visual recovery. These results are discussed in the context of their implication on recovery of amblyopia in adults.

The iPod binocular home‐based treatment for amblyopia in adults: efficacy and compliance

BackgroundOcclusion therapy for amblyopia is predicated on the idea that amblyopia is primarily a disorder of monocular vision; however, there is growing evidence that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression. Furthermore, we have found that a dichoptic treatment intervention designed to directly target suppression can result in clinically significant improvement in both binocular and monocular visual function in adult patients with amblyopia. The fact that monocular improvement occurs in the absence of any fellow eye occlusion suggests that amblyopia is, in part, due to chronic suppression. Previously the treatment has been administered as a psychophysical task and more recently as a video game that can be played on video goggles or an iPod device equipped with a lenticular screen.The aim of this case‐series study of 14 amblyopes (six strabismics, six anisometropes and two mixed) ages 13 to 50 years was to investigate: 1. whether the portable video game treatment is suitable for at‐home use and 2. whether an anaglyphic version of the iPod‐based video game, which is more convenient for at‐home use, has comparable effects to the lenticular version.MethodsThe dichoptic video game treatment was conducted at home and visual functions assessed before and after treatment.ResultsWe found that at‐home use for 10 to 30 hours restored simultaneous binocular perception in 13 of 14 cases along with significant improvements in acuity (0.11 ± 0.08 logMAR) and stereopsis (0.6 ± 0.5 log units). Furthermore, the anaglyph and lenticular platforms were equally effective. In addition, the iPod devices were able to record a complete and accurate picture of treatment compliance.ConclusionThe home‐based dichoptic iPod approach represents a viable treatment for adults with amblyopia.

A double dissociation of the acuity and crowding limits to letter identification, and the promise of improved visual screening

Here, we systematically explore the size and spacing requirements for identifying a letter among other letters. We measure acuity for flanked and unflanked letters, centrally and peripherally, in normals and amblyopes. We find that acuity, overlap masking, and crowding each demand a minimum size or spacing for readable text. Just measuring flanked and unflanked acuity is enough for our proposed model to predict the observer's threshold size and spacing for letters at any eccentricity. We also find that amblyopia in adults retains the character of the childhood condition that caused it. Amblyopia is a developmental neural deficit that can occur as a result of either strabismus or anisometropia in childhood. Peripheral viewing during childhood due to strabismus results in amblyopia that is crowding limited, like peripheral vision. Optical blur of one eye during childhood due to anisometropia without strabismus results in amblyopia that is acuity limited, like blurred vision. Furthermore, we find that the spacing:acuity ratio of flanked and unflanked acuity can distinguish strabismic amblyopia from purely anisometropic amblyopia in nearly perfect agreement with lack of stereopsis. A scatter diagram of threshold spacing versus acuity, one point per patient, for several diagnostic groups, reveals the diagnostic power of flanked acuity testing. These results and two demonstrations indicate that the sensitivity of visual screening tests can be improved by using flankers that are more tightly spaced and letter like. Finally, in concert with Strappini, Pelli, Di Pace, and Martelli (submitted), we jointly report a double dissociation between acuity and crowding. Two clinical conditions-anisometropic amblyopia and apperceptive agnosia-each selectively impair either acuity A or the spacing:acuity ratio S/A, not both. Furthermore, when we specifically estimate crowding, we find a double dissociation between acuity and crowding. Models of human object recognition will need to accommodate this newly discovered independence of acuity and crowding.

Randomised controlled trial of intermittent photic stimulation for treating amblyopia in older children and adults

The treatment of amblyopia is reviewed and it is noted that in addition to conventional 'passive treatment' in children with occlusion, it has been argued that 'active treatment' may be effective in older children and adults. Intermittent photic stimulation (IPS) is one such active treatment. In Study 1, we report a clinical audit of 21 patients treated with IPS, which demonstrated that the maximum improvement is reached after 6 half hour sessions. Study 2 is a double-masked randomised controlled trial comparing IPS with a control treatment in 30 participants aged 10-57 years. Using a sensitive staircase measure of visual acuity (VA), the IPS group improved by about one line (p = 0.0053). The mean improvement was significantly greater (unpaired t-test, p = 0.022) in the IPS group (mean 0.096; S.E.M. 0.029) than in the control group (mean 0.019; S.E.M. 0.022). The improvement occurred in participants with strabismic amblyopia, but not in those with anisometropic amblyopia. Follow up data after about 1 year showed that VA had regressed to pre-treatment levels. The results are discussed within the context of another development in active amblyopia therapy, perceptual learning. The literature on this therapy reveals improvements in VA of about 2.5 lines in older children and adults with anisometropic amblyopia. It is concluded that perceptual learning is likely a better treatment option than IPS for anisometropic amblyopes, and probably also for strabismic amblyopes although a randomised controlled trial is required. It is noted that the existence of effective treatments for adults does not detract from the need to treat amblyopia in younger children.

A new binocular approach to the treatment of Amblyopia in adults well beyond the critical period of visual development

The present treatments for amblyopia are predominantly monocular aiming to improve the vision in the amblyopic eye through either patching of the fellow fixing eye or visual training of the amblyopic eye. This approach is problematic, not least of which because it rarely results in establishment of binocular function. Recently it has shown that amblyopes possess binocular cortical mechanisms for both threshold and suprathreshold stimuli. We outline a novel procedure for measuring the extent to which the fixing eye suppresses the fellow amblyopic eye, rendering what is a structurally binocular system, functionally monocular. Here we show that prolonged periods of viewing (under the artificial conditions of stimuli of different contrast in each eye) during which information from the two eyes is combined leads to a strengthening of binocular vision in strabismic amblyopes and eventual combination of binocular information under natural viewing conditions (stimuli of the same contrast in each eye). Concomitant improvement in monocular acuity of the amblyopic eye occurs with this reduction in suppression and strengthening of binocular fusion. Furthermore, in a majority of patients tested, stereoscopic function is established. This provides the basis for a new treatment of amblyopia, one that is purely binocular and aimed at reducing suppression as a first step.

Is the Selective Serotonin Reuptake Inhibitor Fluoxetine a Fountain of Youth?

Evaluation of: Maya Vetencourt JF, Sale A, Viegi A et al.: The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science 320, 385–288 (2008). The potential for synaptic strength to be regulated by experience is high early in postnatal life, and declines thereafter. The constraint of synaptic plasticity in the adult visual system is thought to underlie the resistance to therapy for the treatment of amblyopia. However, a recent report by Maya Vetencourt et al. demonstrates that systemic administration of the popular antidepressant fluoxetine reactivates synaptic plasticity in the visual system of adult rats, and enables the recovery of function in an eye chronically deprived of vision. Fluoxetine administration stimulated a decrease in basal levels of extracellular GABA, an increase in the level of BDNF and the return of long-term potentiation in slices of visual cortex. The ability to reactivate robust synaptic plasticity in the adult mammalian visual system has clear therapeutic potential for the treatment of amblyopia in adults.

Recovery from amblyopia in adults via decreased visual cortical inhibition caused by experience in an enriched environment

Recovery from amblyopia in adults via decreased visual cortical inhibition caused by experience in an enriched environment

Research in binocular vision and amblyopia: recent progress and future challenges

Aim: To review recent advances in our knowledge about the primary visual cortex and animal models of amblyopia and discuss their relevance for current treatment strategies and speculate about alternative future methods. Methods: A literature-based review was carried out to highlight recent progress and future challenges in research in binocular vision and amblyopia. Results: Amblyopia is the most common develop­mental disorder of vision, resulting from abnormal visual experience during a critical period early in life. It Is associated with physiological and anatomical changes (plasticity) in the primary visual cortex, which are deemed largely irreversible in adulthood. The classical animal model of amblyopia is mono­cular deprivation (MD) by eyelid suture, but induced or naturally occurring strabismus has also been studied extensively. In recent years, research has concentrated on understanding the neural mechan­isms of binocular integration and of cortical plasticity during the critical period, as well as on exploring new avenues for extending plasticity into adulthood. Three lines of animal research arc presented. First, the optimisation of eye-patching regimens to achieve the best possible visual acuity in both eyes; second, the neurophysiology of strabismic suppression; and third, new strategics for treating amblyopia in adolescents and adults, by means of cither visual training paradigms or drug therapies aimed at restoring cortical plasticity after Ihc end of the critical period. Conclusion: The results of the research both comple­ment clinical experience and provide a hopeful outlook for improved or novel methods of treating amblyopia in the future.